Descrizione del progetto
Specie reattive dell’ossigeno nel differenziamento cellulare
Le specie reattive dell’ossigeno (ROS, Reactive Oxygen Species) sono derivati dell’ossigeno molecolare, sottoprodotti tossici del metabolismo strettamente associati allo stress ossidativo. Tuttavia, bassi livelli di ROS prodotti nei mitocondri (mROS) fungono da segnali per i normali processi biologici. Il progetto MitoSignal, finanziato dal Consiglio europeo della ricerca, studierà il modo in cui gli mROS stimolano la differenziazione cellulare. I ricercatori utilizzeranno i parassiti Trypanosoma, gli agenti causali della malattia del sonno, come semplice organismo modello contenente un singolo mitocondrio che subisce vari cambiamenti metabolici durante lo sviluppo programmato. I risultati di MitoSignal forniranno importanti approfondimenti sull’interazione tra i mitocondri e il resto della cellula nelle decisioni sul destino cellulare.
Obiettivo
Mitochondria perform three essential functions: ATP production, metabolite synthesis and cellular signaling. These signals, communicating the bioenergetic and biosynthetic fitness of the organelle to the nucleus, play a powerful role in determining cellular fate. The incorporation of mitochondrial reactive oxygen species (mROS) in cellular signaling is an interesting evolutionary outcome, as excess levels of these potent oxidizers have been implicated in many pathologies. While most research focuses on these outcomes of oxidative stress, much less is known about how mROS drive a range of physiological responses. Furthermore, the available studies are limited to a few traditional model organisms, featuring complex cellular systems with numerous mitochondria at different energetic states. Here, we propose to utilize the unicellular parasites, Trypanosoma brucei and T. congolense, as simplified but elegant models to define mROS-driven cellular differentiation. As these protists undergo programmed development between several distinct life cycle forms, there are striking changes to the structure and physiology of their single mitochondrion that manifest in elevated ROS levels. Importantly, we demonstrated that these ROS molecules are essential for the developmental progression of the parasite. Employing these well-chosen models and combining next-generation biosensors, advanced bioenergetic methods, redox proteomics and a CRISPR/Cas9 genetic screen, we will answer the following fundamental questions: Does mROS drive Trypanosoma cellular differentiation? What molecular processes are responsible for the elevated mROS levels during differentiation? How is the redox signal propagated to the rest of the cell? The proposed research aspires to unravel the fundamental mechanisms underlying the intricate communication between mitochondria and the rest of the cell, featuring cellular hallmarks of cell fate decisions.
Campo scientifico
- engineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensorsbiosensors
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- medical and health sciencesbasic medicinepathology
- medical and health sciencesbasic medicinephysiology
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
ERC - Support for frontier research (ERC)Istituzione ospitante
370 05 Ceske Budejovice
Cechia